The objective of this research is to determine the factors which regulate the total CoA content of heart and liver, the rate of synthesis of CoA from its vitamin precursor, pantothenate, the rate of CoA degradation, and the existence of effective pantothenate storage pools in tissues. Glucagon (or glucagon-insulin ratios) have been implicated in the regulation of CoA content of liver in in vivo studies with alloxan-diabetic and fasted rats, and in studies with rat hepatocytes maintained in primary culture. The mechanism of the regulation is now being investigated in a culture system, and appears to involve cAMP, protein synthesis and activation of pantothenate kinase. Genetically diabetic mice will be compared to control mice to determine the metabolic consequences of altered CoA levels. Restriction of dietary pantothenate will be used to vary liver CoA levels in vivo independently of hormonal states so that the metabolic or pathological consequences of elevated liver total CoA in the diabetic can be determined.